The present invention relates to a method for preparing a hydroxyapatite composite that has a composition similar to that of bone, and that is useful as various kinds of artificial tissues for living organisms such as artificial bone, as well as medical materials. The present invention also relates to a biocompatible material utilizing the composite obtained by the above method.
Natural bone and teeth are molecular composites of inorganic hydroxyapatite (HAp) and collagen, arranged in a three-dimensional matrix. For repairing damaged bone and teeth, it is known to use biocompatible ceramics. Examples of such ceramics include xe2x80x9cBioglassxe2x80x9d (trade name, manufactured by NIPPON ELECTRIC GLASS CO., LTD., OTSU. SIGA, JAPAN) composed of Na2Oxe2x80x94CaOxe2x80x94SiO2xe2x80x94P2O5 and mainly used as a restorative materials in dental surgery, sintered HAp (Ca10(PO4)6(OH)2) mainly used as a bone filling material, and crystallized glass containing apatite and wollastonite (CaOxe2x80x94SiO2) (trade name xe2x80x9cCerabone A-Wxe2x80x9d manufactured by NIPPON ELECTRIC GLASS CO., LTD., OTSU SIGA, JAPAN) used for an artificial otoconite or an ilium spacer.
There has been an attempt to have such ceramics formed on the surface of a matrix having high strength, such as a metal matrix, for use as a substitute for natural bone. Also, in an attempt to produce a flexible, durable material that can be used as artificial tissue for living organisms other than bone, there has been developed a so-called biomimetic process, a method for forming HAp on the surface of readily processible polymer matrices.
The biomimetic process includes the steps of introducing glass particles composed mainly of CaO and SiO2 in an aqueous solution having the ion concentration equivalent to that of human body fluid (simulated body fluid), soaking a polymer matrix in the simulated body fluid to have a number of apatite nuclei formed on the surface of the polymer matrix, and then soaking the matrix in an aqueous solution having the ion concentration 1.5 times that of the simulated body fluid for reaction. It has been reported that according to the biomimetic process, the apatite nuclei grow on the polymer matrix, and a compact and homogeneous bone-like HAp layer is formed with an intended thickness (J.Biomed.Mater.Res.Vol.29, p349-357(1995)).
In the biomimetic process, however, the growth speed of HAp is so slow that even the reaction for as long as more than two weeks cannot generate sufficient amount of HAp on the polymer matrix for use as artificial bone.
As a new method for hydroxyapatite synthesis, there has been proposed alternate soaking process wherein a matrix is soaked in a calcium ion aqueous solution and subsequently in a phosphate ion aqueous solution, and this alternate soaking cycle is repeated to gradually form HAp.
When the alternate soaking process is used for forming HAp on a general-purpose polymer matrix such as of polyethylene, nylon, or silicone, the resulting HAp is mostly amorphous, with a small portion of crystalline HAp. In addition, the bonding strength of the obtained HAp to the polymer matrix is sometimes insufficient.
It is believed that formation of bone-like structures requires the steps of (a) adsorption of inorganic ions by polymer chains, (b) formation of initial HAp crystals as nuclei, (c) formation of HAp layers, and (d) formation of molecular polymer composites. In the alternate soaking process using a general-purpose polymer matrix, the step (b) may be achieved relatively easily, but it is difficult to proceed with the process beyond this step.
It is an object of the present invention to provide a method for preparing a HAp composite having the composition and crystal structure similar to those of natural bone, and expected to have superior affinity, which method enables extremely rapid and efficient formation of HAp on a polymer or metal matrix with excellent bonding strength therebetween.
It is another object of the present invention to provide a biocompatible material that has HAp having the composition and structure similar to those of natural bone, that is expected to have superior affinity, and that has excellent bonding strength between the HAp and the matrix.
According to the present invention, there is provided a method for preparing a hydroxyapatite composite comprising alternately soaking a matrix which has been made hydrophilic at least on its surface (sometimes referred to as matrix (C) hereinbelow), in a calcium ion aqueous solution containing calcium ions and substantially free of phosphate ions (sometimes referred to as calcium ion aqueous solution (A) hereinbelow) and in a phosphate ion aqueous solution containing phosphate ions and substantially free of calcium ions (sometimes referred to as phosphate ion aqueous solution (B) hereinbelow) to securely form hydroxyapatite at least on the surface of the said matrix.
According to the present invention, there is also provided the above method further comprising, after soaking the matrix (C) in the calcium ion aqueous solution (A), removing the calcium ion aqueous solution (A) remaining on the matrix (C) before soaking the matrix (C) in the phosphate ion aqueous solution (B)
According to the present invention, there is also provided the above method further comprising, after soaking the matrix (C) in the phosphate ion aqueous solution (B), removing the phosphate ion aqueous solution (B) remaining on the matrix (C) before soaking the matrix (C) in the calcium ion aqueous solution (A).
According to the present invention, there is further provided a biocompatible material consisting essentially of a hydroxyapatite composite prepared in accordance with the above method.